The present invention relates to a preventive, alleviative or remedy for hypertension which has excellent blood pressure lowering effects, blood-pressure-rise suppressing effects and safety and is available in the form of a food or pharmaceutical.
Examples of a pharmaceutical used for treatment of hypertension include various neuroleptics acting on the neural-factor-related regulator system, ACE inhibitors acting on the heurohumoral-factor-related regulator system, AT receptor antagonists, Ca antagonists acting on the vascular-endothelium-derived-substance-related regulator system, and hypotensive diuretics acting on the body-fluid-regulator system in the kidney. These pharmaceuticals are mainly used in medical institutions for patients suffering from severe hypertension.
Under the present state, however, pharmaceuticals used as a measure against hypertension are a serious burden for patients because in spite of satisfactory effectiveness, their side effects are not a few.
In the case where hypertension is regarded as a life-style related disease, on the other hand, general therapies for improving the life style such as dietetic therapy, kinesitherapy and limitation of alcoholic intake or smoking are applied widely not only to the people having a high normal blood pressure including a mild case but also to patients suffering from severe hypertension. With a tendency to recognize the importance of general therapies, improvement of eating habits has received great attention. Since there exist a large number of foods having blood pressure lowering action, pressure reducing materials derived from foods have so far been briskly searched for and separation and identification of their effective ingredients have been carried out frequently.
Under such situations, there is an increasing demand for the development of a method for preventing, ameliorating or treating hypertension without depending on pharmaceuticals if possible. As such a method, dietetic therapy is particularly important, so that foods having blood pressure lowering effects or blood-pressure-rise inhibitory effects have briskly been searched for. Proposed is use of, as a hypotensor, the juice of an unripe fruit of apples, pears, peaches or like fruits belonging to the family Rosaceae which juice contains fruit polyphenol such as caffeine acid having angiotensin I converting enzyme (ACE) inhibiting action (Japanese Patent Application Laid-Open (Kokai) No. Hei 8-259453). It is also reported that a water extract of sugarcane root tuber contains a chlorogenic acid, which is a polyphenol, and it has ACE inhibitory action (Food Research Results Information, No. 9, 20-21(1997)).
Foods which are said to have pressure reducing effects or their effective ingredients, however, tend to be not always satisfactory in their effectiveness, intake frequency or taste upon intake and in addition, many of them do not start exhibition of blood pressure lowering effects soon after intake.
An object of the present invention is therefore to provide a preventive, alleviative or remedy for hypertension which is derived from plants or foods, has excellent safety, does not become a burden for patients when administered daily and orally, and has high antihypertensive action.
The present inventors have searched for various food- or plant-derived components useful for the prevention or amelioration of hypertension. As a result, it has been found that an extract of coffee beans containing caffeine which is a stimulant has high pressure reducing action and can suitably be formed into a pharmaceutical or food.
In the present invention, there is thus provided a preventive, ameliorant or remedy for hypertension, which comprises an extract of coffee beans; and a food containing the extract.
The extract of coffee beans to be used in the present invention is an extract from coffee beans which are fruits of a coffee tree. As the coffee tree, any one of C. arabica, C. robusta, C. liberica and C. arabusta is usable.
As the coffee beans to be extracted in the present invention, either raw beans or decaffeine treated beans or roasted beans are usable, with raw beans being particularly preferred.
Examples of the method for extracting, from coffee beans, an ingredient effective for the prevention, amelioration or treatment of hypertension include solvent extraction and supercritical fluid extraction. The extract obtained from coffee beans may be purified or may be adjusted by treatment with an ion exchange resin or the like (for example, Japanese Patent Application Laid-Open (Kokai) No. Hei 4-145048, Japanese Patent Application Laid-Open (Kokai) No. Hei 4-145049, etc.).
Examples of the extracting solvent used for solvent extraction include water and hydrophilic organic solvents such as methanol, ethanol, 2-propanol, acetone and methyl ethyl ketone. As the extracting solvent, a water-containing hydrophilic organic solvent having a water content of 5 wt. % (which will hereinafter be called %, simply) or greater, particularly, hydrous ethanol.
The extract of coffee beans to be used in the present invention contains various substances such as known already for example polysaccharides, lipids, chlorogenic acids, proteins, caffeine, minerals and fatty acids etc. It preferably contains chlorogenic acids and caffeine at a weight ratio of 2 or greater, preferably 2 to 1000, more preferably 2.5 to 500, especially 2.5 to 100 from the viewpoints of effects for preventing, ameliorating or treating hypertension, and sour taste with astringency upon intake. Caffeine suppresses pungency and chlorogenic-acid-induced sourness, whereby such a taste is attained. The components of the coffee bean extract may be adjusted to fall within the above-described range by the addition of chlorogenic acid or caffeine.
Examples of the chlorogenic acid include those having caffeine acid ester-bonded to one or two hydroxy groups, at the 3-, 4- or 5-position of quinic acid. Specific examples include 3-caffeoylquinic acid (chlorogenic acid) having caffeine acid ester-bonded to the hydroxyl group at the 3-position of quinic acid; 5-caffeoylquinic acid having caffeine acid ester-bonded to the hydroxyl group at the 5-position of quinic acid; 4-caffeoylquinic acid (cryptochlorogenic acid) having caffeine acid ester-bonded to the hydroxyl group at the 4-position of quinic acid; and isochlorogenic acids having caffeine acid ester-bonded to two hydroxyl groups, among hydroxyl groups at the 3-, 4- and 5-positions of quinic acid (ex. 3,5-caffeoylquinic acid). Salts of them are also embraced in the term xe2x80x9cchlorogenic acidxe2x80x9d used herein.
No particular limitation is imposed on the salts of a chlorogenic acid insofar as they are pharmaceutically acceptable salts. Examples include salts of an alkali (alkaline earth) metal such as sodium, potassium, calcium and magnesium. The chlorogenic acid exists also as a salt in naturally-occurring substances.
The preventive, ameliorant or remedy for hypertension according to the present invention may further contain another antihypertensive (agents) materials (such as xcex1-blocker, xcex2-blocker, xcex1xcex2-blocker, ACE inhibitor, angiotensin II receptor antagonist, Ca blocker, diuretic, or psychotropic agent); vitamin (such as Vitamin A, Vitamin B1, B2, B6, B12, Vitamin C, Vitamin D or Vitamin E); and another active ingredient having blood pressure lowering action [physiologically active substance (ex. high unsaturated fatty acids of xcfx89-3 type such as xcex1-linolenic acid, EPA or DHA, triglyceride and/or diglyceride having this fatty acid as a component fatty acid, catechin which is a tea polyphenol or polymer thereof, or rutin which is a buckwheat polyphenol), Litchi Chinensis Sonn., ginkgo tree, Zizyphi Fructus, Polygonati Rhizoma, Cassiae Semen, Cortinellus shiitake, Momovdicae grosvenori, flowers of Chrysanthemum morifolium, leaves of Samallanthus sonchifolius, mulberry leaves, leaves of Banaba (Lagestroemia speciosa), Senpo, Plantaginis semen, and these extract etc.]
When used as a medicament, the preventive, ameliorant or remedy for hypertension according to the present invention can be formed into an oral administrable composition by adding thereto a pharmaceutically acceptable carrier. Examples of the oral administrable composition include tablets, granules, fine subtilaes, pills, powders, capsules (hard capsules and soft capsules), troches, chewables and liquid preparations (medical drink).
The preventive, ameliorant or remedy for hypertension according to the present invention is available as a food by adding thereto another component. Examples include foods in a liquid, emulsion or paste form such as beverage, soy sauce, milk, yogurt and miso to which ordinarily employed food additives have been added; semi-solid foods such as jelly and gummy; solid foods such as gum, tofu and supplement; powdery foods. Although it is available in any form, beverages, particularly soft drinks, are preferred.
An effective administration amount of the coffee bean extract of the present invention is preferably 5 to 5000 mg, especially 10 to 500 mg, a day per adult (weight: 60 kg) in terms of a chlorogenic acid contained in a dry solid content of the coffee bean extract.